Pharmacologic Principles - The upper limit in MW is determined
Pharmacology- derived from the Greek word
pharmakon- (“poison” in classic Greek, “drug” in
modern Greek); -
- Logia “study of ”
- body of knowledge concerned with the action
of chemicals on biologic systems
Medical Pharmacology- area of pharmacology
concerned with the use of chemicals in the prevention,
diagnosis, and treatment of disease
Toxicology- area of pharmacology concerned with the
undesirable effects of chemicals on biologic systems
Pharmacotherapeutics- the use of medications to
prevent, treat, cure, or alleviate symptoms of disease.
- Pharmacotherapeutics incorporate
pharmacokinetics in which it explains the
clinical purpose or indication for giving the
drug.
Pharmacokinetics -effects of the body on drugs
(absorption, distribution, metabolism, excretion)
- What does the body do to the drug
Pharmacodynamics- actions of the drug on the body
- What does the drug do to the body?
Drugs- Substances that act on biologic systems at the
chemical (molecular) level and alter their functions
- Has a physiological effect when introduced to
the body.
Drug receptors- The molecular components of the
body with which drugs interact to bring about their
effects
DRUG NAMES
Chemical Name– chemical composition and
molecular structure
- Ex: N-(4-Hydroxyphenyl)acetamide
Generic Name (Nonproprietary) – identify
pharmaceutical substances or active pharmaceutical
ingredients
- Ex: acetaminophen/paracetamol
Trade Name (Proprietary)– drug that has trademark;
use of the name is restricted by the drug’s
manufacturer.
- Manufacturer’s given name
- Ex: Biogesic
THE NATURE OF DRUGS
A. Physical Nature of Drugs
a. Solid (eg.Aspirin tablet)
b. Liquid (eg.Nicotine, Ethanol)
c. Gas (eg.Nitrous oxide)
B. Size and Molecular Weight- varies from very
small lithium (MW 7) to very large Thrombolytic
enzymes, antibodies, and other proteins.
primarily by the requirement that drugs must
be able to move within the body. (eg. from
site of administration to the site of action)
C. Drug-Receptor Bonds
a. 3 Major Types of Bonds:
i. Covalent– very strong & irreversible
reaction
ii. Electrostatic – between cation and anion;
weaker than covalent bond
iii. Hydrophobic– quite weak; important in
the interactions of highly lipid-soluble
drugs
● If we wished to design a highly selective short
acting drug for a particular receptor, choose a
molecule that forms weaker bond rather than
reactive molecules that form covalent bonds
D. Drug Shape- permits binding to its receptor site
- Compared to lock and key model, the drug
shape is complementary to that receptor site in
the same way that the key is complementary to
a lock.
- The shape of the drug needs to fit perfectly to
the receptor site in order for it to yield a
response.
a. Chirality -ability of a drug to exist as optically
active stereoisomers or enantiomers.
- its mirror image (it must have one) is
not the same as itself.
E. Rational Drug Design- ability to predict the
appropriate molecular structure of a drug on the
basis of information about its biologic receptor
PHARMACOKINETICS
● The actions of the body on the drug, including
absorption, distribution, metabolism, and
elimination.
● Drugs that we take travel from the site of
administration towards the site of action.
○ E.G. Paracetamol travels from mouth to CNS
in order to induce analgesia.
MOVEMENT OF DRUGS IN THE BODY
PERMEATION- movement of drug molecules into and
within the biological environment
1. Aqueous Diffusion- movement of molecules
through the water extracellular and intracellular
spaces; passive process governed by Fick’s
law which states that the rate of diffusion
across unit area is proportional to the
concentration gradient.
 - Passive- movement from higher BIOAVAILABILITY- the fraction (or percentage) of the
concentration to lower concentration administered dose of drug that reaches the systemic
2. Lipid diffusion- passive movement of circulation
molecules through membranes and other lipid Area under the curve
barriers; governed by Fick’s law 1. (AUC) -The graphic area under a plot of drug
- Applicable for lipid soluble substances concentration versus time after a single dose
3. Transport by special carriers- Drugs that do or during a single
not readily diffuse through membranes may be 2. dosing interval. Units: concentration x time
transported across barriers by mechanisms (eg.mg min/mL)
that carry similar endogenous
substances(eg.Na+/K+ATPase, transporters
for serotonin, norepinephrine, glucose, amino
acids)
- Active- requires a carrier
4. Endocytosis- binding of the transported
molecule to specialized components
(receptors) on cell membranes, with
subsequent internalization by infolding of that
area of the membrane
- Pinocytosis- engulfing the drug particles Peak and Trough Concentrations- The maximum
and minimum drug concentrations achieved during
repeated dosing cycles

VOLUME OF DISTRIBUTION (Vd)- The ratio of the

amount of drug in the body to the drug concentration
in the plasma or blood. Minimum effective concentration (MEC)- The
- Units: Liters plasma drug concentration below which a patient’s
response is too small for clinical benefit

APPLICATION OF PHARMACOKINETICS IN
THERAPEUTICS

CLEARANCE- The ratio of the rate of elimination of a

drug to the concentration of the drug in the plasma or
blood.
- Units: volume/time (eg.mL/min or L/h)

ABSORPTION OF DRUGS
- movement of the drug into the bloodstream
after administration.
ROUTES OF ADMINISTRATION 6. Rectal (suppository) - The rectal route offers
1. Oral (swallowed) - Subject to the first-pass effect partial avoidance of the first-pass effect.
before it reaches the systemic circulation
Pharmaceutical Preparations for Oral 7. Inhalation - Route offers delivery closest to
Administration: respiratory tissues (eg, for asthma). Usually very
a. Tablets- mixture of a drug plus binders and rapid absorption (eg, for anesthetic gases)
fillers, all of which have been compressed
together
b. Enteric-Coated Preparations- consist of 8. Topical - includes application to the skin or to the
drugs that have been covered with a material mucous membrane of the eye, ear, nose, throat,
designed to dissolve in the intestine but not airway, or vagina for local effect
the stomach
- enteric coatings: fatty acids, waxes,
and shellac 9. Transdermal - involves application to the skin for
TWO GENERAL PURPOSES: systemic effect.
i. to protect drugs from acid and pepsin in the
stomach, and
ii. to protect the stomach from drugs that can cause
gastric discomfort
- Disadvantage: absorption can be more
variable than with standard tablets because
gastric emptying time can vary

c. Sustained-Release Preparations- capsules

filled with tiny spheres that contain the actual
drug
- the drug is released steadily throughout
the day
- primary advantage: they permit a
reduction in the number of daily doses
- Disadvantages: high cost; potential for
Factors Affecting Drug Absorption
variable absorption
1. Rate of Dissolution- helps determine the rate of
2. Buccal and sublingual (not swallowed) - Direct
absorption
absorption into the systemic venous circulation
a. Buccal - medicine given between the gums
2. Surface Area- major determinant of the rate of
and the inner lining of the mouth cheek.
absorption
b. Sublingual- the placement of drug under the
- the larger the surface area, the faster
tongue
absorption
3. Intravenous - Instantaneous and complete
absorption (by definition, bioavailability is 100%)
3. Blood Flow- Drugs are absorbed most rapidly
from sites where blood flow is high
- The greater the concentration gradient, the
4. Intramuscular - Often faster and more complete
more rapid absorption will be.
(higher bioavailability) than with oral administration.
4. Lipid Solubility- highly lipid-soluble drugs are
absorbed more rapidly than drugs whose lipid
5. Subcutaneous - Slower absorption than the
solubility is low
intramuscular route.
- lipid-soluble drugs can readily cross the
membranes that separate them from the blood
5. pH Partitioning- Most drugs are weakly acidic or
basic substances and are thus ionized at
physiological pH.
- Passive diffusion across lipophilic membranes
depends on the degree of ionization.
DISTRIBUTION OF DRUGS
- movement of the drug from the circulation to body
tissues.
A. DETERMINANTS OF DISTRIBUTION
a. Size of the organ- determines the concentration
gradient between blood and the organ.
b. Blood flow- well-perfused tissues usually achieve
high tissue concentrations sooner than poorly
perfused tissues
c. Solubility- it influences the concentration of the
drug in the extracellular fluid surrounding the
blood vessels
d. Binding- Binding of a drug to macromolecules in
the blood or a tissue compartment tends to
increase the drug’s concentration in that
compartment.
i. Protein-bound drugs– inactive drug
ii. Highly protein-bound drugs- Drugs that are
more than 90% bound to protein (e.g.,
warfarin, glyburide, sertraline, furosemide,
and diazepam)
iii. Weakly protein-bound drugs - drugs that
are less than 10% bound to protein (e.g.,
gentamicin, metformin, metoprolol, and
lisinopril)
iv. Free drugs - cause pharmacologic
response; active drug
APPARENT VOLUME OF DISTRIBUTION AND
PHYSICAL VOLUMES
Volume of distribution (apparent) - The ratio of the
amount of drug in the body to the drug concentration
in the plasma or blood.
- Units: liters
Exiting the Vascular System
- necessary for drugs to undergo metabolism
and excretion.
A. Typical Capillary Beds- drugs pass between
capillary cells rather than through them
- “large” gaps exist between the cells of the
capillary wall
B. The Blood-Brain Barrier (BBB)- specialized
system of brain microvascular endothelial cells
that shields the brain from toxic substances in the
blood- there
- highly selective and semipermeable
- drugs that are lipid soluble or have a
transport system can cross the BBB
C. Placental Drug Transfer- Membranes of the
placenta do NOT constitute an absolute barrier to
the passage of drugs
- lipid-soluble, nonionized compounds readily
pass from the maternal bloodstream into the
blood of the fetus
METABOLISM OF DRUGS
● Metabolism (or biotransformation)- is the
process by which the body chemically changes
drugs into a form that can be excreted.
○ Liver - primary site of metabolism
○ Drug disposition - a term sometimes
used to refer to metabolism and
elimination of drugs.
○ Cytochrome P450 system - Liver
enzymes which convert drugs to its
metabolites.

A. DRUG METABOLISM AS A MECHANISM OF
ACTIVATION OR TERMINATION OF DRUG
ACTION
Note: Conversion to an inactive metabolite is a form of
elimination.
Prodrugs - are inactive as administered and must be
metabolized in the body to become active.
(eg,clopidogrel, levodopa, minoxidil)
B. DRUG ELIMINATION WITHOUT METABOLISM-
these drugs are not modified by the body; they
continue to act until they are excreted (eg.
Lithium)
Therapeutic Consequences of Drug Metabolism
1. Accelerated renal excretion of drugs- most
important consequence of drug metabolism
a. Kidneys – major organs of drug excretion;
unable to excrete drugs that are highly lipid
soluble
- metabolic conversion can accelerate renal
excretion
2. Drug inactivation
a. Drug metabolism - converts pharmacologically
active compounds to inactive forms
3. Increased therapeutic action
4. Activation of “prodrugs”
5. Increased toxicity
6. Decreased toxicity
Special Considerations in Drug Metabolism
1. Age
a. Infants- drug-metabolizing capacity is limited
- liver does not develop its full capacity to
metabolize drugs until about 1 year after birth
b. Older adults- ability to metabolize drugs may be
decreased
- dose reduction - may be needed to prevent
drug toxicity
2. Induction and Inhibition of Drug-Metabolizing
Enzymes
a. Substrates- drugs that are metabolized by P450
hepatic enzymes
b. Inducers - drugs that act on the liver to increase
rates of drug metabolism
c. Induction - process of stimulating enzyme
synthesis
d. Inhibitors - drugs that act on the liver to decrease
rates of drug metabolism
- Therapeutic consequence: increase in active
drug accumulation due to slower metabolism
3. First-Pass Effect- aka presystemic metabolism or
elimination
- metabolism of drugs or chemicals in liver or
intestine prior to their reaching the systemic
circulation.
- Eg. Nitroglycerin – administered sublingually -
VERY ACTIVE
4. Nutritional Status
a. malnourished patient - drug metabolism may be
compromised
5. Competition Between Drugs- can decrease the
rate at which one or both drugs are metabolized
ELIMINATION OF DRUGS
Drug Elimination - The phase of drug inactivation or
removal from the body by metabolism or excretion
- determines the duration of action for many
drugs
Excretion- mode of elimination for drugs that are not
metabolized

● Drug elimination is not the same as drug

excretion- A drug may be eliminated by
metabolism long before the modified molecules are
excreted from the body.

Renal excretion - predominant means of drug

elimination

Major exception: Volatile anesthetic gases - excreted

primarily by the lungs

A. FIRST-ORDER ELIMINATION- the rate of Dosage Regimens

elimination is proportional to the concentration
- drug’s concentration in plasma decreases
exponentially with time
- half-life of elimination - The concentration of
a drug in the blood will decrease by 50% for
every half-life.
- plan for drug administration over a period of
time
1. Maintenance dose: administered to maintain
a steady state concentration (Css) within the
therapeutic window
2. Loading dose: administered to achieve the
desired plasma level rapidly, followed by a
maintenance dose to maintain the steady state
3. Dose adjustment: The amount of a drug
administered for a given condition is estimated
based on an “average patient.”

B. ZERO-ORDER ELIMINATION- that the rate of

elimination is constant regardless of
concentration
- Such drugs do not have a constant half-life.